Hypoxia induces molecular pathways favoring survival of endometriosis

Hypoxia is a condition characterized by low levels of oxygen that typically occurs in endometriotic lesions; hypoxia induces intracellular pathways that favor the survival of endometriosis.

Key Points

Highlights: 

• Hypoxia is an important impetus for the development of endometriosis. Hypoxia downregulates DUSP2 (Dual-specificity phosphatase-2, an important phosphatase) levels.
• The elevated levels ofIL-6 has been linked to endometriosis-associated infertility, but the underlying mechanisms of this elevation are unknown.
• Hypoxia induces the IL-6 levels by negatively acting on DUSP2; resulting in the survival of the endometriotic cells in the ectopic environment. 

Importance: 

Understanding molecular alterations causing, contributing and sustaining endometriosis may help to control and treatment of the disease.

Key Results:

•  hypoxia-mediated loss of function through intermediary molecules, increase IL- 6 expression
• Increased IL-6 activation then, by other intermediates results in decreased apoptosis and also promotes cell proliferation.

What`s Done Here:

IL-3, STAT3, and DUSP2 levels were evaluated in eutopic and ectopic endometrial cells. Cell proliferation and apoptosis were assessed.

Lay Summary

Kuei-Yang Hsiao and colleagues from the Department of Physiology and the Department of Obstetrics and Gynecology College of Medicine, National Cheng Kung University, Tainan, Taiwan, have investigated the molecular basis of this phenomenon.

In particular, they found that hypoxia significantly suppressed the level of DUSP2 (dual-specificity phosphatase-2), an important phosphatase that specifically inactivates mitogen-activated protein kinase (MAPK). They demonstrated that downregulation of DUSP2 in endometriotic lesions induces the expression of IL-6, a cytokine which is typically elevated in endometriotic tissues and in peritoneal fluids from patients with endometriosis. Increased levels of IL-6 suppress immune surveillance allowing the establishment and sustenance of endometriotic lesions and they are linked to endometriosis-associated infertility. The comprehension of the molecular mechanisms that increase the levels of IL-6 is a very important finding since it represents a future potent therapeutic target. Kuei-Yang Hsiao and colleagues finally demonstrated that IL-6 increased expression causes aberrant activation of STAT3 signaling pathway, which promotes proliferation of stromal cells and prevent them from stress-induced apoptosis, favoring the survival of endometriotic foci under the ectopic environment.